Mixed Lineage Leukemia 1 (MLL1) protein is a member of the SET1 family of histone methyltransferases. Others member of the human SET1 family include MLL2, MLL3, MLL4, SET1a and SET1b. Members of the SET1 family of proteins assemble into multisubunit complexes that regulate mono-, di- and trimethylation of proteins such as H3 histone protein (H3K4). Overproduction of the MLL1 core complex leads to excessive di- and trimethylation of H3K4 which disrupts gene regulation. This, in turn, alters hematopoiesis and normal development and has been linked to certain types of leukemia, solid tumors, and psychotropic disorders, such as schizophrenia and bipolar disorders.
It has been shown that the minimal complex required for di- and trimethylation of H3K4 includes MLL1, WDR5, RbBP5 and Ash2L, which together form the MLL1 core complex. The protein WDR5 has been shown to be critical for these interactions, as it bridges the catalytic SET domain of SET1 family proteins and the regulatory components of RbBP5 and Ash2L. Although the MLL1 core complex is a target of researchers, there are, as of yet, no approaches for inhibit the formation of SET1 family core complexes for the treatment of leukemia and other disorders.